We observed that IL-15 enhances the proliferative response in a dose dependent manner from PBMCs of HIV infected individuals when stimulated by polyclonal mitogen, tetanus toxoid, or HIV specific antigen. The effects of exogenous IL-15 are substantially diminished by adding a neutralizing antibody to the beta chain of the IL-2 receptor. Moreover, the ability of IL-15 to increase proliferation is enhanced by the presence of endogenous IL-2 produced in the cultures. Addition of IL-2 or IL-15 to short term in vitro cultures of either PBMCs or CD4+ T cells had little effect on IL-2, IL-4 or IFNgamma production. By contrast, IL- 12 caused substantial enhancement of both IL-2 and IFNgamma production from these cultures. The role that endogenous cytokines have on IFNgamma induction was also studied. Addition of a neutralizing antibody to the alpha chain of the IL-2 receptor or IL-12 to antigen stimulated cultures caused a striking decrease in IFNgamma production. Neutralization of endogenous IL-15 also resulted in diminished IFNgamma production from cultures stimulated with mitogen. IL-4 and IFNgamma protein production by PBMCs and CD4+ T cells stimulated with mitogen was assessed to see if we could detect a specific bias of cytokine production. Small amounts of IL-4 were detected from CD4+ T cells but not PBMCs from most individuals tested. However, IFNgamma and IL-2 were also produced from these same cultures. The development of multi-drug resistant Tuberculosis has developed into a major health problem. Using the same techniques as outlined above, we will examine the functional capabilities of PBMC's and CD4+ T cells from patients infected with Tuberculosis.